This project will extend our investigations into the etiologic factor(s) and immunopathogenic mechanism(s) involved in A) idiopathic systemic vasculitis and B) chronic urticaria in man. Considerable immunohistological and serologic evidence has been obtained by our group that an immune complex pathogenic mechanism is present in the majority of vasculitis patients (70%) and specific etiologic factors have been implicated in 15%. Future studies will focus on the physicochemical characterization of causal immune complexes and identification of specific etiologic using immunoperoxidase electron microscopy, negative staining electron microscopy and immune complex isolation techniques. The role of IgE and identification of mononuclear cells in the vascular injury process will be assessed. Complement system activation will be determined by Metabolic turnover studies in selected patients. In addition to patients with allergic vasculitis, individuals with myositis will be studied. We have found that chronic urticaria is accompaned by an inflammatory reaction involving postcapillary venules in over 50% of 30 consecutively biopsied patients. Untrastructural analysis, tissues and blood vasomediator concentrations, complement activation, immunologic mechanisms and cutaneous vascular reactivity will be assayed in patients with urticaria and treatment protocols undertaken. This program continues as a collaborative multidisciplinary approach to important clinical diseases with allergic features and has been expanded with additional basic scientists and clinicians as active participants.